Ace1 prevents intracellular copper accumulation by regulating Fet3 expression and thereby restricting Aft1 activity
Abstract
In the yeast Saccharomyces cerevisiae Aft1, the low iron‐sensing transcription factor is known to regulate the expression of the FET 3 gene. However, we found that a strain‐lacking FET 3 is more sensitive to copper excess than a strain‐lacking AFT 1 , and accordingly, FET 3 expression is not fully compromised in the latter. These findings suggest that, under such conditions, another regulator comes into play and controls FET 3 expression. In this work, we identify Ace1, the regulator of copper detoxification genes, as a regulator of FET 3 . We suggest that the activation of FET 3 by Ace1 prevents the hyper activation of Aft1, possibly by assuring the adequate functioning of mitochondrial iron–sulfur cluster biogenesis. While reinforcing the link between iron and copper homeostasis, this work unveils a novel protection mechanism against copper toxicity mediated by Ace1, which relies in the activation of FET 3 and results in the restriction of Aft1 activity as a means to prevent excessive copper accumulation.
- Authors:
-
- Instituto de Tecnologia Química e Biológica António Xavier Universidade Nova de Lisboa Oeiras Portugal
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1433430
- Resource Type:
- Publisher's Accepted Manuscript
- Journal Name:
- Federation of European Biochemical Societies (FEBS) Journal
- Additional Journal Information:
- Journal Name: Federation of European Biochemical Societies (FEBS) Journal Journal Volume: 285 Journal Issue: 10; Journal ID: ISSN 1742-464X
- Publisher:
- Wiley-Blackwell
- Country of Publication:
- United Kingdom
- Language:
- English
Citation Formats
Gaspar‐Cordeiro, Ana, Marques Caetano, Soraia, Amaral, Catarina, Rodrigues‐Pousada, Claudina, and Pimentel, Catarina. Ace1 prevents intracellular copper accumulation by regulating Fet3 expression and thereby restricting Aft1 activity. United Kingdom: N. p., 2018.
Web. doi:10.1111/febs.14450.
Gaspar‐Cordeiro, Ana, Marques Caetano, Soraia, Amaral, Catarina, Rodrigues‐Pousada, Claudina, & Pimentel, Catarina. Ace1 prevents intracellular copper accumulation by regulating Fet3 expression and thereby restricting Aft1 activity. United Kingdom. https://doi.org/10.1111/febs.14450
Gaspar‐Cordeiro, Ana, Marques Caetano, Soraia, Amaral, Catarina, Rodrigues‐Pousada, Claudina, and Pimentel, Catarina. Tue .
"Ace1 prevents intracellular copper accumulation by regulating Fet3 expression and thereby restricting Aft1 activity". United Kingdom. https://doi.org/10.1111/febs.14450.
@article{osti_1433430,
title = {Ace1 prevents intracellular copper accumulation by regulating Fet3 expression and thereby restricting Aft1 activity},
author = {Gaspar‐Cordeiro, Ana and Marques Caetano, Soraia and Amaral, Catarina and Rodrigues‐Pousada, Claudina and Pimentel, Catarina},
abstractNote = {In the yeast Saccharomyces cerevisiae Aft1, the low iron‐sensing transcription factor is known to regulate the expression of the FET 3 gene. However, we found that a strain‐lacking FET 3 is more sensitive to copper excess than a strain‐lacking AFT 1 , and accordingly, FET 3 expression is not fully compromised in the latter. These findings suggest that, under such conditions, another regulator comes into play and controls FET 3 expression. In this work, we identify Ace1, the regulator of copper detoxification genes, as a regulator of FET 3 . We suggest that the activation of FET 3 by Ace1 prevents the hyper activation of Aft1, possibly by assuring the adequate functioning of mitochondrial iron–sulfur cluster biogenesis. While reinforcing the link between iron and copper homeostasis, this work unveils a novel protection mechanism against copper toxicity mediated by Ace1, which relies in the activation of FET 3 and results in the restriction of Aft1 activity as a means to prevent excessive copper accumulation.},
doi = {10.1111/febs.14450},
journal = {Federation of European Biochemical Societies (FEBS) Journal},
number = 10,
volume = 285,
place = {United Kingdom},
year = {Tue Apr 17 00:00:00 EDT 2018},
month = {Tue Apr 17 00:00:00 EDT 2018}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1111/febs.14450
https://doi.org/10.1111/febs.14450
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 2 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
The Role of the Yap5 Transcription Factor in Remodeling Gene Expression in Response to Fe Bioavailability
journal, May 2012
- Pimentel, Catarina; Vicente, Cristina; Menezes, Regina Andrade
- PLoS ONE, Vol. 7, Issue 5
A Permease-Oxidase Complex Involved in High-Affinity Iron Uptake in Yeast
journal, March 1996
- Stearman, R.; Yuan, D. S.; Yamaguchi-Iwai, Y.
- Science, Vol. 271, Issue 5255
Copper-induced binding of cellular factors to yeast metallothionein upstream activation sequences.
journal, January 1989
- Huibregtse, J. M.; Engelke, D. R.; Thiele, D. J.
- Proceedings of the National Academy of Sciences, Vol. 86, Issue 1
Intracellular Copper Does Not Catalyze the Formation of Oxidative DNA Damage in Escherichia coli
journal, December 2006
- Macomber, L.; Rensing, C.; Imlay, J. A.
- Journal of Bacteriology, Vol. 189, Issue 5
Saccharomyces cerevisiae mutants altered in vacuole function are defective in copper detoxification and iron-responsive gene transcription
journal, December 1997
- Szczypka, Mark S.; Zhu, Zhiwu; Silar, Philippe
- Yeast, Vol. 13, Issue 15
Iron-regulated DNA binding by the AFT1 protein controls the iron regulon in yeast.
journal, July 1996
- Yamaguchi-Iwai, Y.; Stearman, R.; Dancis, A.
- The EMBO Journal, Vol. 15, Issue 13
Identification of the Copper Regulon in Saccharomyces cerevisiae by DNA Microarrays
journal, August 2000
- Gross, Claudia; Kelleher, Mark; Iyer, Vishwanath R.
- Journal of Biological Chemistry, Vol. 275, Issue 41
The Fe(II) permease Fet4p functions as a low affinity copper transporter and supports normal copper trafficking in Saccharomyces cerevisiae
journal, October 2000
- Hassett, Richard; Dix, David R.; Eide, David J.
- Biochemical Journal, Vol. 351, Issue 2
Copper Differentially Regulates the Activity and Degradation of Yeast Mac1 Transcription Factor
journal, January 1998
- Zhu, Zhiwu; Labbé, Simon; Peña, Ma. Marjorette O.
- Journal of Biological Chemistry, Vol. 273, Issue 3
Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper–transporting ATPase
journal, January 1993
- Vulpe, Christopher; Levinson, Barbara; Whitney, Susan
- Nature Genetics, Vol. 3, Issue 1
Enhanced Effectiveness of Copper Ion Buffering by CUP1 Metallothionein Compared with CRS5 Metallothionein in Saccharomyces cerevisiae
journal, August 1996
- Jensen, Laran T.; Howard, William R.; Strain, Jeffrey J.
- Journal of Biological Chemistry, Vol. 271, Issue 31
A single amino acid change in CUP2 alters its mode of DNA binding.
journal, September 1990
- Buchman, C.; Skroch, P.; Dixon, W.
- Molecular and Cellular Biology, Vol. 10, Issue 9
Aft2p, a Novel Iron-regulated Transcription Activator That Modulates, with Aft1p, Intracellular Iron Use and Resistance to Oxidative Stress in Yeast
journal, July 2001
- Blaiseau, Pierre-Louis; Lesuisse, Emmanuel; Camadro, Jean-Michel
- Journal of Biological Chemistry, Vol. 276, Issue 36
ACE1 regulates expression of the Saccharomyces cerevisiae metallothionein gene.
journal, July 1988
- Thiele, D. J.
- Molecular and Cellular Biology, Vol. 8, Issue 7
Two distinctly regulated genes are required for ferric reduction, the first step of iron uptake in Saccharomyces cerevisiae.
journal, May 1994
- Georgatsou, E.; Alexandraki, D.
- Molecular and Cellular Biology, Vol. 14, Issue 5
The CUP2 gene product regulates the expression of the CUP1 gene, coding for yeast metallothionein.
journal, January 1989
- Welch, J.; Fogel, S.; Buchman, C.
- The EMBO Journal, Vol. 8, Issue 1
Copper at the Front Line of the Host-Pathogen Battle
journal, September 2012
- Festa, Richard A.; Thiele, Dennis J.
- PLoS Pathogens, Vol. 8, Issue 9
Cuprous oxidase activity of yeast Fet3p and human ceruloplasmin: implication for function
journal, October 2003
- Stoj, Christopher; Kosman, Daniel J.
- FEBS Letters, Vol. 554, Issue 3
Molecular characterization of a copper transport protein in S. cerevisiae: An unexpected role for copper in iron transport
journal, January 1994
- Dancis, Andrew; Yuan, Daniel S.; Haile, David
- Cell, Vol. 76, Issue 2
Sequence, mapping and disruption ofCCC2, a gene that cross-complements the Ca2+-sensitive phenotype ofcsg1 mutants and encodes a P-type ATPase belonging to the Cu2+-ATPase subfamily
journal, March 1995
- Fu, Dadin; Beeler, Troy J.; Dunn, Teresa M.
- Yeast, Vol. 11, Issue 3
[4Fe-4S] Cluster Assembly in Mitochondria and Its Impairment by Copper
journal, January 2017
- Brancaccio, Diego; Gallo, Angelo; Piccioli, Mario
- Journal of the American Chemical Society, Vol. 139, Issue 2
A Physiological Role for Saccharomyces cerevisiae Copper/Zinc Superoxide Dismutase in Copper Buffering
journal, December 1995
- Joh, H. -D.
- Journal of Biological Chemistry, Vol. 270, Issue 50
Homeostatic Regulation of Copper Uptake in Yeast via Direct Binding of MAC1 Protein to Upstream Regulatory Sequences of FRE1 and CTR1
journal, July 1997
- Yamaguchi-Iwai, Yuko; Serpe, Mihaela; Haile, David
- Journal of Biological Chemistry, Vol. 272, Issue 28
MAC1, a nuclear regulatory protein related to Cu-dependent transcription factors is involved in Cu/Fe utilization and stress resistance in yeast.
journal, December 1993
- Jungmann, J.; Reins, H. A.; Lee, J.
- The EMBO Journal, Vol. 12, Issue 13
TheAFT1 Transcriptional Factor is Differentially Required for Expression of High-Affinity Iron Uptake Genes inSaccharomyces cerevisiae
journal, June 1997
- Casas, Celia; Aldea, MartÍ; Espinet, Carme
- Yeast, Vol. 13, Issue 7
A new efficient gene disruption cassette for repeated use in budding yeast
journal, July 1996
- Guldener, U.
- Nucleic Acids Research, Vol. 24, Issue 13
Defects in the Yeast High Affinity Iron Transport System Result in Increased Metal Sensitivity because of the Increased Expression of Transporters with a Broad Transition Metal Specificity
journal, August 1998
- Li, Liangtao; Kaplan, Jerry
- Journal of Biological Chemistry, Vol. 273, Issue 35
Metals, Toxicity and Oxidative Stress
journal, May 2005
- Valko, M.; Morris, H.; Cronin, M.
- Current Medicinal Chemistry, Vol. 12, Issue 10
The CUP2 gene product, regulator of yeast metallothionein expression, is a copper-activated DNA-binding protein.
journal, September 1989
- Buchman, C.; Skroch, P.; Welch, J.
- Molecular and Cellular Biology, Vol. 9, Issue 9
The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity
journal, May 2009
- Macomber, L.; Imlay, J. A.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 20
Copper binding in IscA inhibits iron-sulphur cluster assembly in E scherichia coli : Copper-mediated inhibition of iron-sulphur cluster assembly in
journal, July 2014
- Tan, Guoqiang; Cheng, Zishuo; Pang, Yilin
- Molecular Microbiology, Vol. 93, Issue 4
The YEASTRACT database: an upgraded information system for the analysis of gene and genomic transcription regulation in Saccharomyces cerevisiae
journal, October 2013
- Teixeira, Miguel Cacho; Monteiro, Pedro Tiago; Guerreiro, Joana Fernandes
- Nucleic Acids Research, Vol. 42, Issue D1
Coordinated Remodeling of Cellular Metabolism during Iron Deficiency through Targeted mRNA Degradation
journal, January 2005
- Puig, Sergi; Askeland, Eric; Thiele, Dennis J.
- Cell, Vol. 120, Issue 1
Gene expression profiling and phenotype analyses of S. cerevisiae in response to changing copper reveals six genes with new roles in copper and iron metabolism
journal, August 2005
- van Bakel, Harm; Strengman, Eric; Wijmenga, Cisca
- Physiological Genomics, Vol. 22, Issue 3
ACE1 transcription factor produced in Escherichia coli binds multiple regions within yeast metallothionein upstream activation sequences.
journal, January 1990
- Evans, C. F.; Engelke, D. R.; Thiele, D. J.
- Molecular and Cellular Biology, Vol. 10, Issue 1
Activation of the Iron Regulon by the Yeast Aft1/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis
journal, January 2005
- Rutherford, Julian C.; Ojeda, Luis; Balk, Janneke
- Journal of Biological Chemistry, Vol. 280, Issue 11
Yeast protective response to arsenate involves the repression of the high affinity iron uptake system
journal, May 2013
- Batista-Nascimento, Liliana; Toledano, Michel B.; Thiele, Dennis J.
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1833, Issue 5
Yeast metallothionein. Sequence and metal-binding properties.
journal, November 1985
- Winge, D. R.; Nielson, K. B.; Gray, W. R.
- Journal of Biological Chemistry, Vol. 260, Issue 27
Repression of the Low Affinity Iron Transporter Gene FET4 : A NOVEL MECHANISM AGAINST CADMIUM TOXICITY ORCHESTRATED BY YAP1 VIA ROX1
journal, June 2015
- Caetano, Soraia M.; Menezes, Regina; Amaral, Catarina
- Journal of Biological Chemistry, Vol. 290, Issue 30
The Yeast Fre1p/Fre2p Cupric Reductases Facilitate Copper Uptake and Are Regulated by the Copper-modulated Mac1p Activator
journal, May 1997
- Georgatsou, Elena; Mavrogiannis, Lampros A.; Fragiadakis, George S.
- Journal of Biological Chemistry, Vol. 272, Issue 21
Cooperation of Two mRNA-Binding Proteins Drives Metabolic Adaptation to Iron Deficiency
journal, June 2008
- Puig, Sergi; Vergara, Sandra V.; Thiele, Dennis J.
- Cell Metabolism, Vol. 7, Issue 6
A widespread transposable element masks expression of a yeast copper transport gene.
journal, August 1996
- Knight, S. A.; Labbe, S.; Kwon, L. F.
- Genes & Development, Vol. 10, Issue 15
Low-affinity copper transporter CTR2 is regulated by copper-sensing transcription factor Mac1p in Saccharomyces cerevisiae
journal, April 2012
- Liu, Lihua; Qi, Jin; Yang, Zemin
- Biochemical and Biophysical Research Communications, Vol. 420, Issue 3
The FET4 gene encodes the low affinity Fe(II) transport protein of Saccharomyces cerevisiae
journal, October 1994
- Dix, D. R.; Bridgham, J. T.; Broderius, M. A.
- Journal of Biological Chemistry, Vol. 269, Issue 42
The Wilson disease gene is a putative copper transporting P–type ATPase similar to the Menkes gene
journal, December 1993
- Bull, Peter C.; Thomas, Gordon R.; Rommens, Johanna M.
- Nature Genetics, Vol. 5, Issue 4
Fre1p Cu 2+ Reduction and Fet3p Cu 1+ Oxidation Modulate Copper Toxicity in Saccharomyces cerevisiae
journal, September 2003
- Shi, Xiaoli; Stoj, Christopher; Romeo, Annette
- Journal of Biological Chemistry, Vol. 278, Issue 50
ACE1, a copper-dependent transcription factor, activates expression of the yeast copper, zinc superoxide dismutase gene.
journal, October 1991
- Gralla, E. B.; Thiele, D. J.; Silar, P.
- Proceedings of the National Academy of Sciences, Vol. 88, Issue 19